Screening, Diagnosis, and Management of Primary Aldosteronism

Who Should Be Screened

Patients with hypertension and hypokalemia (spontaneous or substantial diuretic‑induced) should be screened for primary aldosteronism using the plasma aldosterone‑to‑renin ratio (ARR) 【@3】.
Individuals with resistant hypertension, regardless of potassium level, merit ARR screening 【@1】.
An incidentally discovered adrenal mass on imaging warrants ARR testing 【@4】.
A family history of early‑onset hypertension or stroke before age 40 is an indication for screening 【@3】.
Hypertensive patients with obstructive sleep apnea should be screened 【@5】.
Stage 2 hypertension may be considered for broader ARR screening 【@2】.

Normal serum potassium does not exclude primary aldosteronism because hypokalemia is absent in the majority of cases and has low negative predictive value 【@3】【@4】.

A positive ARR is defined as ARR > 30 (aldosterone ng/dL ÷ renin activity ng/mL/h) and plasma aldosterone ≥ 10 ng/dL 【@3】【@4】.
Test preparation includes unrestricted dietary sodium intake and correction of hypokalemia to the normal range 【@4】.
While withdrawal of mineralocorticoid receptor antagonists for ≥ 4 weeks is ideal, newer guidelines allow more flexibility and suggest holding ACE inhibitors, ARBs, or diuretics when feasible 【@6】.

IV saline suppression test: Infuse 2 L of normal saline over 4 h; primary aldosteronism is confirmed if post‑infusion aldosterone > 280 pmol/L. Contraindicated in severe uncontrolled hypertension or heart failure 【@8】.
Captopril suppression test: Administer 25–50 mg captopril; lack of ≥ 30 % aldosterone suppression makes primary aldosteronism unlikely 【@8】.
Exception to confirmatory testing: When ARR > 1400 pmol/L/ng/mL/h and plasma aldosterone > 440 pmol/L (especially with spontaneous hypokalemia), confirmatory testing may be omitted because the probability of unilateral disease is very high 【@8】.

Imaging (CT or MRI) is used to identify adrenal structural abnormalities 【@9】【@7】【@8】.
Adrenal venous sampling (AVS) is essential before surgery to differentiate unilateral from bilateral disease; it should be performed in experienced centers with > 90 % technical success 【@9】.
- A corrected aldosterone/cortisol ratio > 4 : 1 on AVS indicates a unilateral source 【@9】.
- Relying on CT alone is insufficient: 21 % of patients would be inappropriately excluded from surgery and 25 % might undergo unnecessary surgery without AVS 【@9】.
- AVS may be omitted in patients < 40 years old with a solitary adrenal adenoma on CT 【@9】【@10】.

Laparoscopic unilateral adrenalectomy is the treatment of choice for aldosterone‑producing adenoma or unilateral hyperplasia 【@9】【@7】【@10】.
- > 90 % of operated patients experience substantial improvement in hypertension 【@5】.
- 30–60 % achieve complete cure of hypertension, with higher rates in younger patients and those with shorter disease duration 【@4】.
- Surgery leads to improved cardiovascular and renal outcomes compared with medical therapy 【@7】.

Mineralocorticoid receptor antagonists (MRAs) are first‑line therapy 【@5】【@7】【@11】【@10】.
- Spironolactone
  - Starting dose 25–50 mg daily 【@8】; maximum dose 400 mg daily 【@4】.
  - Common adverse effects: gynecomastia, impotence (men); menstrual irregularities (women); hyperkalemia 【@10】.
- Eplerenone
  - Starting dose 50 mg twice daily 【@5】; maximum dose 200–300 mg daily (requires 2–3 × spironolactone dose) 【@5】.
  - Advantage: no anti‑androgenic side effects 【@5】.
  - Efficacy comparable to spironolactone when titrated appropriately 【@5】.
Monitoring: Check serum potassium and creatinine regularly, especially when MRAs are combined with ACE inhibitors or ARBs 【@8】.
Alternative agents for patients intolerant to MRAs: amiloride 2.5–10 mg twice daily or triamterene 100 mg twice daily 【@11】.
Genetic forms (e.g., glucocorticoid‑remediable aldosteronism) are managed with night‑time dexamethasone or prednisone to suppress ACTH 【@11】.

Primary aldosteronism independently increases cardiovascular morbidity and mortality 【@9】【@7】【@10】【@1】【@2】.
- Stroke: 2.8‑fold higher risk 【@1】【@2】【@5】.
- Heart failure: 2.0‑fold higher risk 【@1】【@2】.
- Atrial fibrillation: 4.0‑fold higher risk 【@1】【@2】.
- Coronary artery disease: 1.7‑fold higher risk 【@1】【@2】.
- Chronic kidney disease risk is increased 【@7】【@1】【@2】.
- Associated with myocardial fibrosis, left‑ventricular hypertrophy, and endothelial dysfunction 【@7】.
Both surgical and medical treatments reverse these adverse cardiovascular effects; surgery may provide greater long‑term reduction in left‑ventricular mass 【@7】【@10】【@7】.